Stability Testing of Beclomethasone Dipropionate Nanoemulsion

Purpose: To perform stability studies on a nanoemulsion formulation containing beclomethasone dipropionate (BD) and prepared by spontaneous emulsification method.Method: A nanoemulsion (o/w) containing BD was prepared using eucalyptus oil, Tween-40, ethanol and distilled water. The nanoemulsions were characterized by droplet size, pH, viscosity, conductivity and refractive index. Stability studies were performed according to International Council on Harmonization (ICH) guidelines over a period of 3 months. Droplet size, pH, viscosity, conductivity and refractive index were determined monthly for 3 months. The shelf-life of the nanoemulsion formulation was determined by accelerated stability testing.Results: The droplet size, conductivity, viscosity, pH and refractive index of the optimized formulations did not change significantly (p ≥ 0.05) after 3 months of storage at room temperature (25 ºC). The shelf life was 1.83 years at room temperature.Conclusion: The study demonstrates that the physical and chemical stability of BD is enhanced when it is formulated as a nanoemulsion.Keywords: Nanoemulsion, Beclomethasone dipropionate, Shelf-life, Accelerated stability, Viscosity, Conductivity, Refractive inde

Bayesian inversion of synthetic AVO data to assess fluid and shale content in sand-shale media

Reservoir characterization of sand-shale sequences has always challenged geoscientists due to the presence of anisotropy in the form of shale lenses or shale layers. Water saturation and volume of shale are among the fundamental reservoir properties of interest for sand-shale intervals, and relate to the amount of fluid content and accumulating potentials of such media. This paper suggests an integrated workflow using synthetic data for the characterization of shaley-sand media based on anisotropic rock physics (T-matrix approximation) and seismic reflectivity modelling. A Bayesian inversion scheme for estimating reservoir parameters from amplitude vs. offset (AVO) data was used to obtain the information about uncertainties as well as their most likely values. The results from our workflow give reliable estimates of water saturation from AVO data at small uncertainties, provided background sand porosity values and isotropic overburden properties are known. For volume of shale, the proposed workflow provides reasonable estimates even when larger uncertainties are present in AVO data

Impact of disasters, including pandemics, on cardiometabolic outcomes across the life-course: a systematic review

BackgroundDisasters are events that disrupt the daily functioning of a community or society, and may increase long-term risk of adverse cardiometabolic outcomes, including cardiovascular disease, obesity and diabetes. The objective of this study was to conduct a systematic review to determine the impact of disasters, including pandemics, on cardiometabolic outcomes across the life-course.DesignA systematic search was conducted in May 2020 using two electronic databases, EMBASE and Medline. All studies were screened in duplicate at title and abstract, and full-text level. Studies were eligible for inclusion if they assessed the association between a population-level or community disaster and cardiometabolic outcomes ≥1 month following the disaster. There were no restrictions on age, year of publication, country or population. Data were extracted on study characteristics, exposure (eg, type of disaster, region, year), cardiometabolic outcomes and measures of effect. Study quality was evaluated using the Joanna Briggs Institute critical appraisal tools.ResultsA total of 58 studies were included, with 24 studies reporting the effects of exposure to disaster during pregnancy/childhood and 34 studies reporting the effects of exposure during adulthood. Studies included exposure to natural (n=35; 60%) and human-made (n=23; 40%) disasters, with only three (5%) of these studies evaluating previous pandemics. Most studies reported increased cardiometabolic risk, including increased cardiovascular disease incidence or mortality, diabetes and obesity, but not all. Few studies evaluated the biological mechanisms or high-risk subgroups that may be at a greater risk of negative health outcomes following disasters.ConclusionsThe findings from this study suggest that the burden of disasters extend beyond the known direct harm, and attention is needed on the detrimental indirect long-term effects on cardiometabolic health. Given the current COVID-19 pandemic, these findings may inform public health prevention strategies to mitigate the impact of future cardiometabolic risk.PROSPERO registration numberCRD42020186074.</jats:sec

Efficacy of proprioceptive neuromuscular facilitation techniques versus traditional prosthetic training for improving ambulatory function in transtibial amputees

Abstract The objective of this randomized controlled trial was to evaluate the efficacy of proprioceptive neuromuscular facilitation (PNF) techniques in comparison to traditional prosthetic training (TPT) in improving ambulatory function in transtibial amputees. Thirty study participants (19 men and 11 women) with unilateral transtibial amputation participated in the study. They were randomly allocated to either the traditional training group (i.e., TPT) (n Z 15) or the PNF training group (n Z 15). The treatment in the TPT group consisted of weight-bearing, weight-shifting, balance, and gait exercises for 30 minutes daily for 10 treatment sessions. In the PNF group, the same activities were performed by employing PNF principles and techniques. The outcome measures were gait parameters (e.g., stride width, step length, and stride length) and the Locomotor Capabilities Index (LCI). The between-group comparisons at the end of the trial showed that the PNF group showed significant improvement in gait parameters and in the LCI, compared to the TPT group (p &lt; 0.05). The results of the study suggested that prosthetic training based on proprioceptive feedback is more effective than the traditional prosthetic programme in improving ambulatory function

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Monte Carlo simulations of membrane signal transduction events: Effect of receptor blockers on G-protein activation

Cells have evolved elaborate strategies for sensing, responding to, and interacting with their environment. In many systems, interaction of cell surface receptors with extracellular ligand can activate cellular signal transduction pathways leading to G-protein activation and calcium mobilization. In BC 3 H1 smooth muscle-like cells, we find that the speed of calcium mobilization as well as the fraction of cells which mobilize calcium following phenylephrine stimulation is dependent upon receptor occupation. To determine whether receptor inactivation affects calcium mobilization, we use the receptor antagonist prazosin to block a fraction of cell surface receptors prior to phenylephrine stimulation. For cases of equal receptor occupation by agonist, cells with inactivated or blocked receptors show diminished calcium mobilization following phenylephrine stimulation as compared to cells without inactivated receptors. Ligand/receptor binding and two-dimensional diffusion of receptors and G-proteins in the cell membrane are studied using a Monte Carlo model. The model is used to determine if receptor inactivation affects G-protein activation and thus the following signaling events for cases of equal equilibrium receptor occupation by agonist. The model predicts that receptor inactivation by antagonist binding results in lower G-protein activation not only by reducing the number of receptors able to bind agonist but also by restricting the movement of agonist among free receptors. The latter process is important to increasing the access of bound receptors to G-proteins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43997/1/10439_2006_Article_BF00000009.pd

Diurnal Variations of Mouse Plasma and Hepatic Bile Acid Concentrations as well as Expression of Biosynthetic Enzymes and Transporters

Diurnal fluctuation of bile acid (BA) concentrations in the enterohepatic system of mammals has been known for a long time. Recently, BAs have been recognized as signaling molecules beyond their well-established roles in dietary lipid absorption and cholesterol homeostasis.The current study depicted diurnal variations of individual BAs detected by ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) in serum and livers collected from C57BL/6 mice fed a regular chow or a chow containing cholestyramine (resin). Circadian rhythms of mRNA of vital BA-related nuclear receptors, enzymes, and transporters in livers and ilea were determined in control- and resin-fed mice, as well as in farnesoid X receptor (FXR) null mice. The circadian profiles of BAs showed enhanced bacterial dehydroxylation during the fasting phase and efficient hepatic reconjugation of BAs in the fed phase. The resin removed more than 90% of BAs with β-hydroxy groups, such as muricholic acids and ursodeoxycholic acid, from serum and livers, but did not exert as significant influence on CA and CDCA in both compartments. Both resin-fed and FXR-null mouse models indicate that BAs regulate their own biosynthesis through the FXR-regulated ileal fibroblast growth factor 15. BA flux also influences the daily mRNA levels of multiple BA transporters.BA concentration and composition exhibit circadian variations in mouse liver and serum, which influences the circadian rhythms of BA metabolizing genes in liver and ileum. The diurnal variations of BAs appear to serve as a signal that coordinates daily nutrient metabolism in mammals

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. METHODS: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. FINDINGS: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. INTERPRETATION: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades